What is Potassium?
Potassium is the primary intracellular cation in the body.
Potassium Distribution
- Intracellular: 98% of total body potassium (inside cells)
- Extracellular: Only 2% of total body potassium (in serum/plasma)
- Measured value: Serum potassium reflects only the small extracellular fraction
Why Is Potassium Tightly Regulated?
Serum potassium concentration is tightly regulated (3.5-5.0 mEq/L) because:
- Small deviations = big problems: Even minor changes outside the narrow range can be life-threatening
- Cardiac risk: Abnormal potassium causes dangerous arrhythmias
- Neuromuscular risk: Affects muscle and nerve function throughout the body
Critical Functions of Potassium
- Cardiac conduction: Maintains resting membrane potential; critical for normal cardiac rhythm
- Neuromuscular excitability: Essential for nerve impulse transmission and muscle contraction
- Cellular metabolism: Required for protein synthesis, glycogen formation, enzyme function
- Acid-base balance: Participates in hydrogen ion exchange
- Insulin secretion: Required for normal pancreatic beta-cell function
Both hypokalemia and hyperkalemia can cause fatal arrhythmias. Severe potassium disturbances (K <2.5 or >6.5 mEq/L) with ECG changes constitute medical emergencies requiring immediate intervention.
Test Description
What is Potassium?
Potassium is the primary intracellular cation in the body.
Potassium Distribution
- Intracellular: 98% of total body potassium (inside cells)
- Extracellular: Only 2% of total body potassium (in serum/plasma)
- Measured value: Serum potassium reflects only the small extracellular fraction
Why Is Potassium Tightly Regulated?
Serum potassium concentration is tightly regulated (3.5-5.0 mEq/L) because:
- Small deviations = big problems: Even minor changes outside the narrow range can be life-threatening
- Cardiac risk: Abnormal potassium causes dangerous arrhythmias
- Neuromuscular risk: Affects muscle and nerve function throughout the body
Critical Functions of Potassium
- Cardiac conduction: Maintains resting membrane potential; critical for normal cardiac rhythm
- Neuromuscular excitability: Essential for nerve impulse transmission and muscle contraction
- Cellular metabolism: Required for protein synthesis, glycogen formation, enzyme function
- Acid-base balance: Participates in hydrogen ion exchange
- Insulin secretion: Required for normal pancreatic beta-cell function
Both hypokalemia and hyperkalemia can cause fatal arrhythmias. Severe potassium disturbances (K <2.5 or >6.5 mEq/L) with ECG changes constitute medical emergencies requiring immediate intervention.
Hypokalemia (K <3.5 mEq/L)
Hypokalemia is common, affecting up to 20% of hospitalized patients. It results from inadequate intake, transcellular shifts, or excessive losses (renal or GI).
Classification by Severity
| Severity | Potassium Level | Clinical Features |
|---|---|---|
| Mild | 3.0-3.5 mEq/L | Usually asymptomatic; fatigue, muscle weakness may occur |
| Moderate | 2.5-3.0 mEq/L | Muscle weakness, cramps, constipation, polyuria, ECG changes |
| Severe | <2.5 mEq/L | Severe weakness, paralysis, ileus, rhabdomyolysis, arrhythmias |
Causes of Hypokalemia
1. Transcellular Shift (K Moves Into Cells)
- Insulin: Promotes K uptake into cells (DKA treatment, insulin overdose)
- Beta-2 agonists: Albuterol, epinephrine, stress/catecholamine surge
- Alkalosis: Metabolic or respiratory alkalosis drives K into cells
- Refeeding syndrome: Insulin surge with refeeding after starvation
- Hypothermia: Intracellular shift during cooling
- Hypokalemic periodic paralysis: Rare genetic disorder
2. Renal Losses (Urine K >15-20 mEq/L)
Diuretics (Most Common):
- Loop diuretics (furosemide, bumetanide)
- Thiazide diuretics (hydrochlorothiazide, chlorthalidone)
Mineralocorticoid Excess:
- Primary hyperaldosteronism (Conn's syndrome)
- Cushing's syndrome (excess cortisol has mineralocorticoid activity)
- Licorice ingestion (glycyrrhizic acid inhibits 11β-HSD, mimics aldosterone)
Renal Tubular Disorders:
- Renal tubular acidosis (Type 1 and Type 2)
- Bartter syndrome, Gitelman syndrome (genetic)
- Fanconi syndrome
Other:
- Hypomagnesemia (impairs K retention; must correct Mg to correct K)
- Amphotericin B (nephrotoxic)
- Osmotic diuresis (hyperglycemia, mannitol)
3. GI Losses (Urine K <15 mEq/L)
- Diarrhea: Most common GI cause (K-rich stool)
- Vomiting/NG suction: Direct HCl loss + secondary hyperaldosteronism from volume depletion
- Laxative abuse: Chronic laxative use
- Villous adenoma: Secretes K-rich fluid
- VIPoma: Vasoactive intestinal peptide-secreting tumor causing severe diarrhea
4. Inadequate Intake
- Malnutrition, anorexia nervosa
- Alcoholism
- Elderly with poor diet
Note: Inadequate intake alone rarely causes severe hypokalemia because kidneys can reduce K excretion to <15 mEq/day
ECG Changes in Hypokalemia
| K Level | ECG Findings |
|---|---|
| 3.0-3.5 mEq/L | • Flattened T waves • Prominent U waves (best seen in V2-V3) |
| 2.5-3.0 mEq/L | • ST depression • T wave inversion • Prolonged QT interval (actually QU interval) |
| <2.5 mEq/L | • Severe ST depression • Ventricular ectopy (PVCs) • Risk of torsades de pointes, VT, VF |
Treatment of Hypokalemia
- IV potassium chloride: 10-20 mEq/hour via central line (max 40 mEq/hour for life-threatening arrhythmias)
- Continuous cardiac monitoring: Required during rapid IV replacement
- Check and replace magnesium: Hypokalemia refractory to replacement if Mg is low
- Avoid dextrose-containing fluids: Insulin secretion will worsen hypokalemia
Mild-Moderate Hypokalemia:
- Oral potassium: Preferred for K >2.5 mEq/L (20-40 mEq PO q6-8h)
- IV potassium (peripheral): Max 10 mEq/hour via peripheral IV (causes phlebitis if faster)
- Address underlying cause: Stop diuretics, replace magnesium, treat diarrhea
- Dietary sources: Bananas, oranges, potatoes, spinach (adjunct, not primary treatment)
Hyperkalemia (K >5.5 mEq/L)
Hyperkalemia is less common than hypokalemia but more immediately life-threatening due to risk of fatal arrhythmias. It results from decreased renal excretion, transcellular shifts, or excessive intake.
Classification by Severity
| Severity | Potassium Level | Clinical Significance |
|---|---|---|
| Mild | 5.5-6.0 mEq/L | Usually asymptomatic; monitor and address cause |
| Moderate | 6.0-7.0 mEq/L | ECG changes likely; muscle weakness possible |
| Severe | >7.0 mEq/L | Medical emergency; high risk of cardiac arrest |
Pseudohyperkalemia = falsely elevated K due to K release from cells during/after blood draw:
- Hemolysis: Most common cause (pink/red serum)
- Prolonged tourniquet time: Fist clenching, difficult draw
- Thrombocytosis: Platelets >1,000,000/µL release K during clotting
- Leukocytosis: WBC >100,000/µL (leukemia)
If suspected, repeat sample with careful technique. Patient will be asymptomatic and ECG normal.
Causes of Hyperkalemia
1. Decreased Renal Excretion (Most Common)
Kidney Disease:
- Acute kidney injury (AKI) - most common true cause
- Chronic kidney disease (CKD) with GFR <20 mL/min
- End-stage renal disease (ESRD)
Medications (Very Common):
- RAAS inhibitors: ACE inhibitors, ARBs, direct renin inhibitors
- Potassium-sparing diuretics: Spironolactone, amiloride, triamterene
- NSAIDs: Decrease renin and aldosterone
- Heparin: Decreases aldosterone synthesis
- Trimethoprim, pentamidine: Block renal K secretion
- Calcineurin inhibitors: Tacrolimus, cyclosporine
Hypoaldosteronism:
- Addison's disease (primary adrenal insufficiency)
- Type 4 RTA (hyporeninemic hypoaldosteronism) - common in diabetics
2. Transcellular Shift (K Exits Cells)
- Acidosis: Metabolic acidosis (K shifts out as H+ moves in)
- Insulin deficiency: DKA, hyperglycemic hyperosmolar state
- Cell lysis: Tumor lysis syndrome, rhabdomyolysis, hemolysis, burns
- Hyperkalemic periodic paralysis: Rare genetic disorder
- Beta-blockers: Non-selective beta-blockers impair cellular K uptake
- Succinylcholine: Causes K release from muscle (avoid in burns, denervation)
- Digitalis toxicity: Inhibits Na-K-ATPase pump
3. Excessive Intake
- IV potassium administration (error, too rapid infusion)
- Salt substitutes (KCl-based) in renal patients
- Potassium-rich foods in CKD/ESRD (rare alone)
- Massive blood transfusion (stored blood has high K)
ECG Changes in Hyperkalemia
ECG changes progress as K rises and are more predictive of cardiac risk than absolute K level:
| K Level | ECG Findings |
|---|---|
| 5.5-6.5 mEq/L | • Tall, peaked T waves (narrow base) • Shortened QT interval |
| 6.5-7.5 mEq/L | • PR prolongation • P wave flattening/loss • QRS widening |
| 7.5-8.0 mEq/L | • Marked QRS widening • "Sine wave" pattern (pre-arrest rhythm) |
| >8.0 mEq/L | • Ventricular fibrillation • Asystole • Cardiac arrest |
Treatment of Hyperkalemia
IMMEDIATE ACTIONS (Cardioprotection):
- Calcium gluconate 10%: 10-20 mL IV over 2-3 min
- Stabilizes cardiac membrane (no effect on K level)
- Effect within 1-3 minutes, lasts 30-60 min
- Repeat if ECG changes persist
SHIFT K INTO CELLS (Temporary Measures):
- Insulin + Dextrose: 10 units regular insulin IV + 25g dextrose (D50W)
- Lowers K by 0.5-1.5 mEq/L
- Onset 15-30 min, peak 30-60 min, duration 4-6 hours
- Monitor glucose (risk of hypoglycemia)
- Albuterol: 10-20 mg nebulized (or 0.5 mg IV)
- Lowers K by 0.5-1.0 mEq/L
- Onset 30 min, duration 2-4 hours
- Synergistic with insulin
- Sodium bicarbonate: 50-100 mEq IV (only if severe metabolic acidosis present)
- Questionable efficacy as sole agent
- Use in acidotic patients (pH <7.1)
REMOVE K FROM BODY (Definitive Therapy):
- Loop diuretics: Furosemide 40-80 mg IV (if adequate renal function)
- Increases renal K excretion
- Ineffective in oliguric AKI or ESRD
- Potassium binders:
- Sodium polystyrene sulfonate (Kayexalate): 15-30g PO/PR (onset 1-2 hours, slow)
- Patiromer (Veltassa): 8.4-25.2g PO daily (non-acute, for chronic hyperkalemia)
- Sodium zirconium cyclosilicate (Lokelma): 10g PO TID (faster onset than patiromer)
- Hemodialysis: Most effective method
- Indications: Severe hyperkalemia refractory to medical therapy, AKI/ESRD, K >7.5-8.0 mEq/L
- Removes 25-50 mEq K per hour
Mild Hyperkalemia (5.5-6.0 mEq/L, No ECG Changes):
- Dietary potassium restriction (<2g/day)
- Discontinue offending medications (ACE-I, ARBs, K-sparing diuretics, NSAIDs)
- Loop diuretics if adequate renal function
- Treat underlying cause (optimize renal function, correct acidosis)
- "Peaked T waves = hyperkalemia until proven otherwise": Tall, narrow-based, symmetric T waves are the earliest and most specific ECG finding.
- ECG trumps lab value: A K of 6.2 with peaked T waves is more concerning than K of 7.0 with normal ECG. Treat based on ECG changes, not just the number.
- Hypokalemia + diuretics = dangerous arrhythmia risk: Diuretic-induced hypokalemia significantly increases risk of ventricular arrhythmias, especially in patients on digoxin or with structural heart disease.
- Hypokalemia is often accompanied by hypomagnesemia: Mg deficiency impairs renal K conservation. Always check and replace Mg when treating hypokalemia. "K won't stay up until Mg is corrected."
- Refractory hypokalemia? Think Mg, Mg, Mg: If K replacement isn't working, check magnesium level and replace aggressively (2-4g MgSO4 IV).
- ACE-I + ARB + spironolactone = "triple whammy" for hyperkalemia: Combining RAAS inhibitors dramatically increases hyperkalemia risk, especially in CKD.
- Hemolyzed sample? Repeat before treating: Pink or red serum indicates hemolysis, causing pseudohyperkalemia. Repeat with careful draw. Never treat based on hemolyzed sample alone.
- DKA presents with hyperkalemia, then hypokalemia: Initial hyperkalemia (acidosis, insulin deficiency) masks total body K depletion. K drops precipitously with insulin treatment. Monitor closely and replace early.
- Calcium doesn't lower potassium: Calcium stabilizes cardiac membrane but has zero effect on serum K. It buys time for definitive therapy (insulin, dialysis) to work.
- Sine wave = cardiac arrest imminent: Wide, sine wave-like QRS pattern on ECG indicates extreme hyperkalemia. Give calcium immediately and prepare for crash cart/dialysis.
- Avoid rapid K correction for chronic hypokalemia: Chronic hypokalemia allows cellular adaptation. Rapid correction can cause rebound hyperkalemia, especially in renal impairment.
- Loop diuretics are useless in anuric patients: Furosemide requires urine output to work. In oliguric AKI or ESRD, dialysis is the only reliable method to remove K.
- Normal K doesn't mean normal total body K: Serum K represents <2% of total body K. A patient can have severe total body K depletion with normal serum K (and vice versa during transcellular shifts).
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